A critical issue in managing patients with branch retinal vein occlusion (BVO), central retinal vein occlusion (CRVO), diabetic retinopathy or other types of ischemic retinopathy is the identification of those patients who will go on to develop retinal or iris neovascularization (NV). Retinal ischemia, as defined by capillary non-perfusion on a fluorescein angiogram, is the best known risk factor for the development of NV. At present, however, it is not possible to determine with angiography or clinical observation whether there may be varying degrees of ischemia within areas of capillary non-perfusion. This limitation may explain why only 41% of BVO patients and about 60% of CRVO patients with extensive retinal capillary non-perfusion develop NV. Our studies to date show that the ERG can provide information about the grade of retinal ischemia. From ERG studies we have determined that retina has no observable circulation is not necessarily infarcted, and that sensitivity loss in viable, non-perfused tissue can vary extensively among patients who have similar clinical profiles. Furthermore, our data suggest that only patients demonstrating sufficient ERG-determined sensitivity loss (not ERG amplitude loss) are at risk for the development of neovascularization (NV), thus making the ERG a tool that is potentially more useful than fluorescein angiography in identifying patients that are at risk. We have shown that the ERG is sensitive to detecting the retinal changes that accompany proliferative disease in CRVO. The proposed research will investigate the prognostic value of the ERG in CRVO and diabetic retinopathy in separate prospective studies. Linear discriminant analysis will be performed separately on these groups, in order to determine which ERG and clinical variables maximally discriminate between the proliferative and non-proliferative outcomes. The intriguing finding that much of the retinal sensitivity loss in CRVO is attributable to the photoreceptors will be investigated by measuring a-wave intensity-response functions, and by examining these data in the context of a two-stage ERG model that we have developed. Retinal sensitivity loss in carotid occlusive disease will be characterized, both for its own predictive value and for what it may teach us about the effects of incipient carotid stenosis on retinal function. Carotid and ocular blood flow studies will be performed on selected CRVO patients - some with normal and others with abnormal function in the clinically-normal eye-to determine the relationship between the functional changes and ocular perfusion in these patients.